Immune system modulation of central processing for chronic pain

Abstract

Strategic Research Priority: Bioscience for Health
Abstract
Emerging evidence in animals suggests that environmental enrichment (EE) attenuates chronic pain. Neuroimmune interactions play critical roles in chronic pain development thus with this project we will test the hypothesis that immune cells mediate the positive modulatory effects of EE on central processing for neuropathic pain. Mice will be housed in EE and NE conditions prior the induction of neuropathic pain and then monitored in behavioural studies. Changes in pain thresholds will be linked to specific gene fingerprints of both spinal cord and immune cells. Cell adoptive transfer and chimeric mice will complement these findings.


Project
Novel emerging evidence indicates that life style changes and recreational activity can mitigate chronic pain in man. This is being replicated in preclinical studies in which environmental enrichment (EE: enhanced sensory, motor and cognitive stimulation) can attenuate chronic pain, as compared to normal environment (NE). Neuroimmune interactions play critical roles in mediating chronic pain. Indeed, we and others observed infiltration of T cells in the spinal cord in concomitance to the development of neuropathic pain. Furthermore, both pharmacological immunosuppression and genetic immunodeficiency significantly influence pain development. Our preliminary results on mice housed in EE for two weeks demonstrate an unanticipated change in the gene expression profile of CD4+ T cells as indicated by microarray analysis (61 differentially regulated genes versus NE-derived T cells). Most intriguingly, this was associated with a unique regulatory T cell effector phenotype characterised by a reduced production of IFN-g and increased levels of IL-10. These cells were previously associated with a reduced neuropathic response.
With this project we propose to test the hypothesis that EE impacts on central processing for neuropathic pain through the modulation of the CD4+ T cell response. This hypothesis will be addressed with the following questions:
1. Does EE reduce the development of chronic neuropathic pain?
2. Do CD4+ T cells mediate the effects of EE on neuropathic pain?
3. What is the gene expression profile of both CD4+ T cells and spinal cord tissues following EE?

Mice housed in EE and NE conditions will be monitored over time for the development of pain. CD4+ T cells and spinal cord tissue from the same animals will be used to perform gene expression profiling. The student will learn molecular (qPCR to confirm microarray data) and cellular (FACS, adoptive transfer of immune cells and immunohisto(cyto)chemistry) approaches to complement training in behavioural physiology.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M009513/1 01/10/2015 30/09/2023
1632395 Studentship BB/M009513/1 01/10/2015 23/11/2017 Kelly Elizabeth Woods